This proposal is Christina Springstead Scanlon's first submission for the National Institute of Dental and Craniofacial Research (NIDCR) Individual National Research Service Award (NRSA) Predoctoral Dental Scientist Fellowship (F30). The one year award will allow Christina to continue her graduate education in clinical dentistry and in the Oral Health Sciences PhD Program at the University of Michigan School of Dentistry. Furthermore, the grant will allow her to pursue her career plan to become an independent investigator. The overall objective of this application is to determine the extent to which nuclear factor of activated T-cells cytoplasmic, calcineurin dependent 2 (NFATc2) regulates galanin receptor 2 (GALR2)- mediated progression of head and neck squamous cell carcinoma (HNSCC) via release of inflammatory cytokines. HNSCC is the sixth most common cancer in the world. The survival rate has not changed in more than forty years nor have any novel therapeutic agents been developed. HNSCC tumor cells secrete prostaglandin (PGE2) and matrix metalloproteinase (MMP) 2 and 9, which have an important role in tumor progression. Knowledge of this signaling cascade will facilitate the development of targeted therapeutics. The central hypothesis of this proposal is that GALR2 promotes invasion and migration of HNSCC via downstream activation of NFATc2 with subsequent secretion of PGE2, MMP-2 and MMP-9. The aims of this proposal are: 1) to determine the mechanism by which GalR2 induces NFATc2-mediated cytokine secretion in HNSCC, and 2) to determine the extent to which NFATc2-mediated cytokine secretion promotes invasion of HNSCC in vitro and in vivo. PUBLIC HEALTH RELEVANCE: The research proposed in this grant application will uncover the roles of proteins involved in the migration and invasion of head and neck cancer cells, processes which are important in the disease progression of oral cancer. The goals of this proposal are to develop new treatment strategies for head and neck cancer treatment, as well as to support the career development and research of Christina Springstead Scanlon, a DDS/PhD student who is training to become a clinician-scientist.